Arsenic Methyltransferase and Apolipoprotein E Polymorphism in Pregnant Women Exposed to Inorganic Arsenic in Drinking Water in Western Romania.

Previous studies have shown that inorganic arsenic (iAs) exposure may be associated with genotoxic and cytotoxic effects. The aim of this study was to evaluate the relationship between several polymorphisms in AS3MT and APOE genes and urinary As and the relationship between these polymorphisms and pregnancy loss. We determined urinary As concentrations and performed genotyping analysis in 50 cases of spontaneous pregnancy loss and 50 controls, matched to cases on gestational age. The most frequently identified AS3MT polymorphisms in both cases and controls were in rs10748835 (80% cases and 68% controls), rs3740400 (78% cases and 64% controls), rs7085104 (74% cases and 48% controls), and rs1046778 (62% cases and 54% controls). We identified 30 different haplotypes in AS3MT SNPs, with four predominant haplotypes (>8%). Cases with Haplotype 1 had four-fold higher urinary DMA and two-fold higher MMA concentration than those without this haplotype, the MMA levels were lower in cases and controls with Haplotype 4 compared to Haplotype 1, and the DMA levels were significantly lower in cases with Haplotype 4 compared to Haplotype 3. Cases with Haplotype 1 had higher levels of all analyzed biomarkers, suggesting that Haplotype 1 may be associated with greater exposure to iAs and tobacco smoke. Our results suggest the importance of the AS3MT gene in iAs metabolism among pregnant women with low-level drinking water iAs exposure.

Killer Cell Immunoglobulin-like Receptor Genotypes and Reproductive Outcomes in a Group of Infertile Women: A Romanian Study.

A growing body of evidence suggests that endometrial immune disorders may be responsible for endometrial dysfunctions that can lead to gynecological and obstetrical pathology. The aim of this study was to explore the potential relationship between different killer cell immunoglobulin-like receptor (KIR) genotypes and reproductive outcomes. We conducted a prospective cohort study that included 104 infertile patients undergoing an in vitro fertilization procedure. All participants underwent clinical and ultrasound examination, genetic evaluation (KIR genotyping), endometrial washing fluid sampling for cytokine determination, endometrial tissue sampling for histologic assessment and hysteroscopic evaluation. Our analysis showed statistically significant lower levels of uterine cytokines TNF-α (p = 0.001) and IL-1beta (p = 0.000) in the KIR AA genotype group as compared to KIR AB and BB among study participants with chronic endometritis. The study results suggest that the KIR AA genotype population subgroups may be more susceptible to developing endometrial disorders such as chronic endometritis. The changes in the behavior of NK cells seem to be subtle and expressed as an altered regulatory pattern.

Impact of Follicle Stimulating Hormone Receptor (FSHR) Polymorphism on the Efficiency of Co-Treatment with Growth Hormone in a Group of Infertile Women from Romania.

"Poor responders" (PR) are an important category of infertile women who experience a modest response to controlled ovarian stimulation. In this study, we evaluated response to growth hormone (GH) administration among PR patient subtypes stratified by follicle stimulation hormone receptor (FSHR) polymorphism (c.2039A > G p.Asn680Ser). We conducted a cohort study of 125 women with poor ovarian response, 58 of whom received GH in addition to the standard treatment, and 67 of whom received the standard treatment only. The Ala307Thr polymorphism genotypes were analyzed using a polymerase chain reaction-restriction fragment length polymorphism method, and the FSHR gene polymorphism was analyzed using a predesigned TaqMan SNP Genotyping Assay (rs6166). A comparative analysis detected statistically significant differences in mean mature follicles (p = 0.0002), metaphase-II oocytes (p = 0.0005), progesterone levels (p = 0.0036), and IGF levels (follicle IGF1, p = 0.0004) between GH-treated and non-GH-treated participants with the FSHR (Ser/Ser) polymorphism. However, the differences were modest among participants with the other two FSHR polymorphisms (Ser/Asn and Asn/Asn). The subcategory of patients with the FSHR Asn680Ser (Ser/Ser) polymorphism showed a stronger response when GH was added to the IVF protocol.

Birth defects in Tarnaveni area, Romania - preliminary study results.

BACKGROUND AND AIMS: In the development of any human body, defects may occur, resulting in the occurrence of congenital malformations, also referred to as birth defects. The aim of this preliminary study was to assess the prevalence of birth defects registered during a period of 5 years in Tarnaveni area. As Tarnaveni is located in close proximity to a former chemical plant, a recognized hazardous waste site, we conducted this pilot study to assess the prevalence of birth defects, in order to evaluate the need for a more comprehensive investigation of a potential relation between the exposure to toxic metals contaminating the environmental media as a result of the past industrial activities, and the prevalence of the birth defects in this area. METHODS: We abstracted birth information (gestational age at delivery (GA), birth weight (BW), birth length (BL), head circumference (HC), and major structural birth defects), from medical records at "Dr. Gheorghe Marinescu" Tarnaveni Municipal Hospital, of the 2010-2014 period. We expressed BW as Z-scores relative to expected mean values at each gestational age for a reference population, calculated the ponderal index, and determined the 5 years birth defects prevalence among live births during the study interval. RESULTS: The 5 years (2010-2014) prevalence of birth defects, was 3.3% (95% confidence interval (CI): 2.47, 4.09). There were n = 163 (8.7%) preterm deliveries (less than 37 weeks of gestation at delivery), mean birth weight was 3108.3 g (standard deviation (SD) = 517.1), ranging from 450-4600 g, and n = 187 (10%) were low birth weight (LBW) (less than 2500 g). The ponderal index was 2.2 g/cm3 on average (SD = 0.5), with range 1.2-20.7 g/cm3. CONCLUSIONS: While preliminary, our data show a 5 years (2010-2014) prevalence of major structural birth defects among newborns from Tarnaveni area of 3.3%. These pilot results indicate the need for a more comprehensive investigation of a potential relation between the exposure to toxic metals contaminating the environmental media as a result of the past industrial activities and the prevalence of the birth defects in Tarnaveni area.